WO2020013193A1

WO2020013193A1 - Filter material for removing leukocytes, filter for removing leukocytes and method for producing same

Info

Publication number: WO2020013193A1
Application number: PCT/JP2019/027187
Authority: WO
Inventors: 和也永峰; 貴幸宮本; 武和前田
Original assignee: 株式会社カネカ
Priority date: 2018-07-13
Filing date: 2019-07-09
Publication date: 2020-01-16
Also published as: US20210268415A1; JP7264896B2; JPWO2020013193A1; CN112384260A

Abstract

A filter material for removing leukocytes, said filter material comprising a non-woven fabric configured from polyester fibers, wherein, in a differential scanning calorimetry (DSC) curve obtained by DSC, the non-woven fabric has a first endothermic peak at the melting point and a second endothermic peak with the maximum in a temperature range of 155-225^°C inclusive.

Description

Leukocyte removal filter material, leukocyte removal filter and method for producing the same

The present invention relates to a filter material for removing leukocytes from blood or the like, a leukocyte removal filter provided with the filter material, and a method for producing the same.

血液 Blood products for blood transfusion are products in which leukocytes have been removed in advance before storage for the purpose of reducing transfusion side effects such as pyrogenic reactions and infectious diseases caused by leukocytes. As methods for removing leukocytes from blood and the like, there are generally two types of methods, a centrifugal separation method using a difference in specific gravity of cells and a filter method using a porous material as a filter material, but high leukocyte removal performance by simple operation. Is widely used. One method of removing leukocytes by a filter method is to use a nonwoven fabric as a filter material. Various nonwoven fabrics have been developed as filter materials for leukocyte removal filters, and their thermal performance has been controlled for the purpose of improving leukocyte removal performance. For example, Patent Document 1 discloses a leukocyte removal filter using a nonwoven fabric having a non-crystallization heat of 5 J / g or less before steam heating as a filter material.

International Publication No. WO 2016/204289

The fiber diameter of the non-woven fabric used for the leukocyte removal filter is similar to the size of cells such as blood cells, or in order to form pores smaller than that, it is possible to use ultrafine fibers having a fiber diameter of about 10 μm or 10 μm or less. Desired. In the production of leukocyte removal filters, sterilization is required to kill microorganisms such as pathogens attached in the production process, and steam sterilization is generally used. Therefore, the nonwoven fabric made of ultrafine fibers used for the leukocyte removal filter is used as a filter material after undergoing the heat effect in steam sterilization. The present inventors have studied the leukocyte removal filter disclosed in Patent Document 1, and found that the thermal effect of steam sterilization causes a change in the thermal performance of the nonwoven fabric of the filter material. It has been found that the desired leukocyte removal performance may not be obtained in some cases.

The present invention has been made to solve the above-described problems, and an object of the present invention is to provide a filter material for leukocyte removal and a leukocyte removal filter having excellent leukocyte removal performance.

The present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, completed the present invention. That is, the gist of the present invention is as follows.
[1] A filter material for leukocyte removal, wherein the filter material has a nonwoven fabric composed of polyester fibers, and the nonwoven fabric has a melting point at a melting point in a DSC curve obtained by differential scanning calorimetry (DSC). A filter material having one endothermic peak and a second endothermic peak having a maximum value in a temperature range of 155 ° C or more and 225 ° C or less.
[2] The filter material according to [1], wherein the nonwoven fabric has an elongation in at least one direction of 15% or more.
[3] The filter material according to [2], wherein the elongation is 20% or more.
[4] The filter material according to any one of [1] to [3], wherein the nonwoven fabric comprises 95% by mass or more of the constituent fibers made of polyester fibers.
[5] The filter material according to any one of [1] to [4], wherein the polyester fiber is a polyethylene terephthalate fiber.
[6] The filter material according to any one of [1] to [5], wherein the average fiber diameter of the constituent fibers of the nonwoven fabric is 3 μm or less.
[7] The filter material according to any one of [1] to [6], wherein the nonwoven fabric is a meltblown nonwoven fabric.
[8] A leukocyte removal filter, wherein the filter material according to any one of [1] to [7] is arranged in a filter container.
[9] A method for producing a leukocyte removal filter comprising a filter material having a nonwoven fabric composed of polyester fibers in a filter container,
a) a step of heat-treating the nonwoven fabric composed of polyester fibers in a constrained state at a temperature of 155 ° C. or more and 225 ° C. or less;
b) applying a hydrophilic coating to the non-woven fabric after the heat treatment;
c) arranging a filter material containing the hydrophilic coated nonwoven fabric in a filter container, and sealing the filter container;
d) steam sterilizing the filter disposed in the filter container at a temperature of 100 ° C. or more and 130 ° C. or less;
A method for producing a leukocyte removal filter, comprising:
[10] The method for producing a leukocyte removal filter according to [9], wherein the polyester fiber is a polyethylene terephthalate fiber.
[11] The method for producing a leukocyte removal filter according to [9] or [10], wherein an average fiber diameter of constituent fibers of the nonwoven fabric is 3 μm or less.

The leukocyte removal filter material and leukocyte removal filter of the present invention have excellent leukocyte removal performance. The leukocyte-removing filter material and leukocyte-removing filter of the present invention can stably achieve high performance even after steam sterilization, for example.

4 shows a DSC measurement data chart of the nonwoven fabric of the filter produced in Production Example 1. 9 shows a DSC measurement data chart of the nonwoven fabric of the filter produced in Production Example 2. 9 shows a measurement data chart of DSC of the nonwoven fabric of the filter manufactured in Production Example 3. 13 shows a DSC measurement data chart of the nonwoven fabric of the filter manufactured in Production Example 4. 13 shows a DSC measurement data chart of the nonwoven fabric of the filter manufactured in Production Example 5. 13 shows a measurement data chart of DSC of the nonwoven fabric of the filter produced in Production Example 6.

Hereinafter, specific embodiments of the present invention will be described in detail. The present invention is not limited to the following embodiments at all, and can be implemented with appropriate modifications within the scope of the present invention.

In an embodiment of the present invention, the filter material of the leukocyte removal filter has a nonwoven fabric composed of polyester fibers, and the nonwoven fabric has a first endothermic peak at a melting point in a DSC curve obtained by differential scanning calorimetry (DSC). And a second endothermic peak having a maximum value in a temperature range of 155 ° C. or more and 225 ° C. or less. With such a configuration, the filter material of the present invention exhibits extremely high leukocyte removal performance. In addition, when manufacturing a filter material or a leukocyte removal filter, the change in the thermal characteristics of the nonwoven fabric of the filter material before and after steam sterilization is small, and a filter material having high leukocyte removal performance can be easily manufactured. .

The filter material is used for filtering a liquid containing leukocytes, and examples of the leukocyte-containing liquid include whole blood, bone marrow, umbilical cord blood, menstrual blood, tissue extract, and those obtained by roughly separating them. . The animal species as a source of the leukocyte-containing liquid is not particularly limited, and mammals such as humans, cows, mice, rats, pigs, monkeys, dogs, and cats are preferable.

不織布 The nonwoven fabric forming the filter material is not particularly limited as long as it is at least made of polyester fibers, and it is preferable that polyester fibers are contained as a main component of the constituent fibers of the nonwoven fabric. In the nonwoven fabric of the filter material, 75% by mass or more of the constituent fibers are more preferably made of polyester fibers, more preferably 85% by mass or more, and even more preferably 95% by mass or more.

ポリエステル Examples of the polyester constituting the polyester fiber include polyethylene terephthalate, polytrimethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, and polybutylene naphthalate. Among these, polyethylene terephthalate or polybutylene terephthalate is preferably used, and polyethylene terephthalate is more preferably used. Therefore, it is preferable to use polyethylene terephthalate fiber or polybutylene terephthalate fiber as the polyester fiber constituting the nonwoven fabric, and it is more preferable to use polyethylene terephthalate fiber. In this case, the nonwoven fabric preferably comprises polyethylene terephthalate fibers or polybutylene terephthalate fibers at 75% by mass or more of the constituent fibers, more preferably at least 85% by mass, even more preferably at least 95% by mass.

種類 The type of nonwoven fabric used for the filter material is not particularly limited, and it can be produced by either a wet method or a dry method. In addition, a nonwoven fabric obtained by a melt blowing method, a flash spinning method, or a papermaking method is preferable, and a melt blowing method is more preferable, since a nonwoven fabric made of fibers having a smaller fiber diameter can be obtained. By manufacturing the nonwoven fabric by the melt blow method, it becomes easy to arbitrarily adjust the fiber diameter, the basis weight, the average pore diameter, and the like of the filter material. Therefore, it is preferable to use a melt blown nonwoven fabric as the nonwoven fabric of the filter material.

An example of a method for producing a nonwoven fabric by a melt blow method will be described. The molten polymer melted in the extruder is filtered by a suitable filter, guided to a molten polymer introduction portion of a melt blow die, and then discharged from an orifice-shaped nozzle. At the same time, the heating gas introduced into the heating gas introduction unit is guided to a heating gas ejection slit formed by a melt blow die lip, and is ejected from here to form the above-discharged molten polymer to form ultrafine fibers. Then, a nonwoven fabric is obtained by laminating. At this time, by appropriately selecting and controlling spinning factors such as resin viscosity, melting temperature, discharge amount per single hole, heating gas temperature, heating gas pressure, and distance between the spout and the accumulation net, a desired value can be obtained. A nonwoven fabric having a fiber diameter and a basis weight can be obtained, and fiber orientation and fiber dispersibility can be controlled. Furthermore, it is also possible to control the thickness and average pore diameter of the nonwoven fabric by hot pressing.

The nonwoven fabric of the filter material has a first endothermic peak at a melting point and a second endothermic peak having a maximum value in a temperature range of 155 ° C or more and 225 ° C or less in a DSC curve obtained by differential scanning calorimetry (DSC). . The first endothermic peak is derived from the melting point of the fiber constituting the nonwoven fabric. In the case of polyethylene terephthalate fiber, the first endothermic peak usually shows an endothermic peak derived from the melting point in a temperature range of 250 ° C. to 260 ° C., and the polybutylene terephthalate fiber In this case, an endothermic peak derived from the melting point is usually shown in the temperature range of 220 to 230 ° C. It is considered that the second endothermic peak is caused by a crystal structure having a different stability (size, structure, etc.) from the crystal structure at the melting point. The fact that the nonwoven fabric of the filter material has the second endothermic peak indicates that a plurality of crystal structures exist in the constituent fibers (particularly, polyester fibers) of the nonwoven fabric. The present inventors have investigated the relationship between the filter performance of the filter material and the second endothermic peak by focusing on the second endothermic peak, and found that the maximum value of the second endothermic peak is in a temperature region of 155 ° C or more and 225 ° C or less. It was found that, while recovering erythrocytes in high yield, leukocytes which cause various non-hemolytic side effects when remaining in blood products can be removed at an extremely high removal rate. Then, it has been found that by appropriately adjusting the maximum value of the second endothermic peak, a certain degree of stability can be obtained in a crystal structure different from the crystal structure at the melting point.

The differential scanning calorimetry is performed as follows. Using a differential scanning calorimeter (EXSTAR6000 @ DSC6200R, manufactured by Seiko Instruments Inc.), the nonwoven fabric was taken out from the filter material, and about 4.5 to 5.5 mg of the taken out nonwoven fabric was put into an aluminum pan (5 mm in diameter). The measurement is performed under a nitrogen atmosphere under the conditions of a starting temperature of 30 ° C., an ending temperature of 370 ° C., and a heating rate of 10 ° C./min to obtain a DSC curve.

As described above, in order to obtain a nonwoven fabric having the maximum value of the second endothermic peak in the temperature range of 155 ° C. or more and 225 ° C. or less, the nonwoven fabric may be heat-treated at a predetermined temperature. The lower limit of the heat treatment temperature at this time is preferably 155 ° C, and the upper limit is preferably 225 ° C. The heat treatment time depends on the fiber diameter of the nonwoven fabric, but is preferably adjusted as appropriate between 30 seconds and 1 hour.

The average fiber diameter of the constituent fibers of the nonwoven fabric of the filter material is preferably 10 μm or less, more preferably 5 μm or less, still more preferably 3 μm or less, and still more preferably 2 μm or less, from the viewpoint of enhancing leukocyte removal performance by the filter material. . On the other hand, the lower limit value of the average fiber diameter of the constituent fibers of the nonwoven fabric of the filter material is preferably 0.3 μm or more. This makes it possible to stably produce the nonwoven fabric and to suppress the viscosity resistance from being too high when filtering blood with the filter material. The average fiber diameter refers to a value determined according to the following procedure. That is, a part of the filter material is sampled, the diameters of 100 or more randomly selected fibers are measured based on a scanning electron micrograph, and the average fiber diameter is obtained by number-averaging the diameters. .

不織布 The nonwoven fabric of the filter material preferably has a lower limit of the average pore diameter of 1 μm, more preferably 2 μm. By setting the average pore diameter to 1 μm or more, it becomes easy to shorten the filtration time. On the other hand, the upper limit of the average pore diameter is preferably 10 μm, and more preferably 6 μm. By setting the average pore diameter to 10 μm or less, it becomes easy to ensure the leukocyte removal performance. In addition, the average pore diameter of the nonwoven fabric of the filter material means a mean flow pore size measured by a palm porometer (manufactured by PMI).

The lower limit of the basis weight of the nonwoven fabric of the filter material is preferably 5 g / m ² , and more preferably 20 g / m ² . By setting the basis weight to 5 g / m ² or more, it becomes easy to secure the tensile strength of the filter material. On the other hand, the upper limit of the basis weight of the nonwoven fabric of the filter material is preferably 80 g / m ² , and more preferably 60 g / m ² . By setting the basis weight to 80 g / m ² or less, it is possible to suppress the flow resistance during filtration from being excessively increased, and to easily shorten the filtration time. The basis weight means a value obtained by measuring the weight (g) per unit area (1 m ² ) of the nonwoven fabric.

不織布 The nonwoven fabric of the filter material preferably has an elongation in at least one direction of at least 15%, more preferably at least 20%. This makes it difficult for the nonwoven fabric to break during the production of the filter material or the filtration by the filter material. The nonwoven fabric preferably has a maximum elongation of 15% or more or 20% or more. For example, among the elongations when stretched in four directions different by 45 °, at least the maximum elongation is 15% or more or 20% or more. It should just be. In general, the elongation of the nonwoven fabric is greatest in a TD (Transverse @ Direction) direction orthogonal to a MD (Machine Direction) direction, which is a direction in which the nonwoven fabric flows (takes up) at the time of molding. Although the upper limit of the elongation of the nonwoven fabric is not particularly limited, for example, the maximum elongation is preferably 50% or less, more preferably 35% or less.

伸 The elongation of the nonwoven fabric is measured as follows. The nonwoven fabric is taken out of the filter material, and a test piece is cut out from the taken out nonwoven fabric in a size of 8 mm in width and 40 mm in length. Using a universal testing machine (RTG-1210, manufactured by A & D Corp.), the both ends of the test piece were fixed with chucks, the test piece was pulled at a chuck interval of 20 mm and a pulling speed of 20 mm / min. The distance between the chucks is measured, and the elongation is determined by the following formula: elongation (%) = ((distance between chucks at break of nonwoven fabric−20) / 20) × 100.

不織布 The nonwoven fabric of the filter material may be surface-treated. For example, it is preferable that the surface of the fiber is modified by graft polymerization, polymer coating, chemical treatment with alkali, acid, or the like, plasma treatment, or the like. Among them, the nonwoven fabric is preferably coated with a hydrophilic material, whereby the affinity of the filter material with blood or the like is improved, and the wettability can be improved.

The hydrophilic coating is preferably a polymer coating. According to the polymer coating, the fiber surface can be easily modified into a preferable structure. The polymer used for the polymer coating is not particularly limited as long as it is a hydrophilic polymer, as long as the load on blood components and the like is not particularly large. Examples of the hydrophilic polymer include polymers having a hydrophilic functional group such as a hydroxyl group, an amino group, a carboxyl group, a sulfonic acid group, a carbonyl group, and a sulfonyl group. Among them, copolymers of a monomer such as hydroxyethyl (meth) acrylate having a hydrophilic functional group and dimethylaminoethyl (meth) acrylate or diethylaminoethyl (meth) acrylate having a basic functional group, and polyvinylpyrrolidone, It is particularly preferable because, in addition to improving the wettability of the nonwoven fabric by making the fiber surface hydrophilic, the performance of capturing blood cells such as leukocytes can be improved by introducing a chargeable functional group.

There are no particular restrictions on the method of coating the polymer, as long as it can coat the pores of the filter material, that is, the fiber gaps of the nonwoven fabric, and the nonwoven fabric surface can be uniformly coated within a certain range. A method can be used. Examples of the method include a method of impregnating a non-woven fabric with a solution of a polymer, a method of spraying a solution of a polymer onto a non-woven fabric, and a method of applying and transferring a solution of a polymer to a non-woven fabric using a gravure roll or the like. Above all, a method of impregnating a non-woven fabric with a solution in which a polymer is dissolved is preferable because of excellent continuous productivity and low cost.

The solvent for dissolving the polymer is not particularly limited as long as it does not significantly dissolve the nonwoven fabric of the filter material. Examples thereof include amides such as N, N-dimethylformamide and N, N-dimethylacetamide; sulfoxides such as dimethyl sulfoxide. Alcohols such as methanol, ethanol, propanol and butanol; ketones such as acetone and methyl ethyl ketone; esters such as methyl acetate and ethyl acetate; hydrocarbons such as toluene and cyclohexane; halogenated hydrocarbons such as chloroform and dichloromethane. Water; and a mixture of two or more of these solvents. Among them, alcohols such as methanol, ethanol, propanol, and butanol are preferable, and methanol and ethanol are particularly preferable.

フィルター The filter material of the present embodiment may have only one nonwoven fabric described above, or may have a laminate of a plurality of nonwoven fabrics. Further, an arbitrary nonwoven fabric may be laminated on the nonwoven fabric described above. By laminating a plurality of nonwoven fabrics to form a filter material, leukocyte removal performance can be further improved. In the case of laminating a plurality of nonwoven fabrics, the nonwoven fabrics may be arranged so as to overlap with each other in the flow direction of the leukocyte-containing liquid to be filtered. When laminating a plurality of nonwoven fabrics, the number of laminations is preferably 10 or more, more preferably 20 or more. On the other hand, the upper limit of the number of layers is preferably 60 or less, and more preferably 50 or less, from the viewpoint of shortening the filtration time.

Next, the leukocyte removal filter of the present invention will be described. The leukocyte removal filter of the present invention is one in which the filter material of the present embodiment is disposed in a filter container. The filter container may be provided with only one filter material or a plurality of filter materials. Further, different types of filter materials may be included on the upstream side and the downstream side of the filter material of the present embodiment. For example, by arranging a filter material having a larger basis weight and an average pore diameter than the nonwoven fabric of the present embodiment on the upstream side and functioning as a pre-filter, an effect such as a reduction in filtration time is expected. Furthermore, since the leukocyte-containing liquid often contains substances such as microaggregates that adversely affect the performance of the filter material, it is preferable to remove these substances using a prefilter. As the prefilter, for example, it is preferable to use a continuous porous body having pores having an average pore diameter of 20 μm to 200 μm.

The leukocyte removal filter preferably includes the nonwoven fabric of the present embodiment as a filter material, and the filter material is disposed in a filter container having a liquid inlet and a liquid outlet. The filter container may take any form such as a sphere, a container, a cassette, a bag, a tube, a column, and the like. For example, a cylindrical form having a capacity of about 0.1 mL to 1000 mL and a diameter of about 0.1 cm to 15 cm, or A square or rectangular shape having a length of about 0.1 cm to 20 cm and a square pillar shape having a thickness of about 0.1 cm to 5 cm is preferable. Preferably, the filter container is at least partially transparent or translucent, so that the progress of the filtration can be visually checked.

白 The leukocyte removal filter provided with the filter material of the present embodiment can be manufactured, for example, as follows. That is, a) a step of heat-treating a non-woven fabric composed of polyester fibers in a constrained state at a temperature of 155 ° C. or more and 225 ° C. or less, b) a step of applying a hydrophilic coating to the heat-treated non-woven fabric, and c) a non-woven fabric coated with a hydrophilic coating Disposing the filter material in the filter container and sealing the filter container; d) producing a filter material disposed in the filter container by steam sterilizing at a temperature of 100 ° C. or more and 130 ° C. or less. A leukocyte removal filter having a filter material having a nonwoven fabric made of polyester fibers in a filter container can be manufactured.

In the heat treatment step (a), the nonwoven fabric made of polyester fiber is heat-treated in a constrained state at a temperature of 155 ° C or more and 225 ° C or less. For details of the nonwoven fabric composed of polyester fibers, the above description is referred to. By heat-treating the non-woven fabric composed of polyester fibers at a temperature of 155 ° C. or more and 225 ° C. or less, a non-woven fabric having a DSC curve with a maximum endothermic peak in a temperature range of 155 ° C. or more and 225 ° C. or less is obtained.

In the heat treatment step, it is preferable to perform the heat treatment in a state where the nonwoven fabric is constrained from the viewpoint of preventing a significant shrinkage of the dimensions of the nonwoven fabric during the heat treatment. For example, it is preferable to be in a state of being constrained in one or two axes of the vertical and horizontal axes of the surface of the nonwoven fabric, or in a state of being constrained in the direction of a vertical axis on the surface of the nonwoven fabric. As a method of realizing the constrained state of the surface of the nonwoven fabric in the vertical and horizontal axes, there is a method of fixing the end portion of the nonwoven fabric with a fixture such as a metal frame. As a method of realizing the constrained state in the vertical axis direction on the surface of the nonwoven fabric, there is a method of performing heat treatment in a state of being stacked in a roll shape.

In the coating step of step b), a hydrophilic coating is applied to the heat-treated nonwoven fabric. For details of the hydrophilic coating, reference is made to the above description. The coating step is preferably performed after the nonwoven fabric has been cooled to room temperature after the heat treatment step. For example, it is preferable to cool the nonwoven fabric after the heat treatment over 5 minutes or more.

In the assembling step of step c), a filter material containing a nonwoven fabric coated with hydrophilicity is placed in a filter container, and the filter container is sealed, thereby producing a filter unit. For details of the arrangement of the filter container and the filter material, refer to the above description. In the assembly process, the filter material can be shielded from the outside by sealing the filter container.

滅菌 In the sterilization step of step d), the filter material placed in the filter container is steam-sterilized at a temperature of 100 ° C. or more and 130 ° C. or less. By sterilizing the filter material in the sterilization step, the filter material can be maintained in a high hygiene state until the leukocyte removal filter is used. Steam sterilization can be performed by disposing a filter material to be sterilized in a filter container in a sealed state, and heating the filter material to 100 ° C. or higher with saturated steam. For example, sterilization may be performed at a temperature of about 100 ° C. or more and 130 ° C. or less, such as 121 ° C. for 20 minutes or 118 ° C. for 40 minutes, for a time of about 20 minutes or more and 60 minutes or less.

According to the above manufacturing method, the filter material obtained in the heat treatment step exhibits a high leukocyte removal rate, and even after the sterilization step, the characteristics of the filter material are maintained, and the filter material exhibits a high leukocyte removal rate. . That is, since the thermal performance of the filter material hardly changes due to the thermal influence of steam sterilization, a leukocyte removal filter exhibiting extremely high leukocyte removal performance can be easily manufactured.

This application claims the benefit of priority based on Japanese Patent Application No. 2018-133398 filed on July 13, 2018. The entire contents of the specification of Japanese Patent Application No. 2018-133398 filed on July 13, 2018 are incorporated herein by reference.

Hereinafter, the present invention will be described in detail in examples, but the present invention is not limited to the examples below.

(1) Production example of filter (1-1) Production example 1
Using polyethylene terephthalate (PET), a nonwoven fabric composed of polyethylene terephthalate fibers was produced by a melt blow method. The average fiber diameter of the nonwoven fabric was 1.52 μm, the basis weight was 40 g / m ² , the thickness was 0.42 mm, and the average pore diameter was 3.30 μm. The obtained non-woven fabric was restrained using a metal frame in the longitudinal and horizontal directions of the plane using a metal frame, and placed in a dryer (PH-202, manufactured by ESPEC Corporation) heated to 160 ° C. for 3 minutes. Heat treatment. Then, it was taken out of the dryer and naturally cooled at room temperature to obtain a heat-treated nonwoven fabric.

は Separately from the above, a coating solution was prepared as follows. First, 0.95 mol / L of 2-hydroxyethyl methacrylate and 0.05 mol / L of 2-dimethylaminoethyl methacrylate were added to special grade ethanol to make a total volume of 300 mL. As a polymerization initiator, 2,2′-azobis (2,4-dimethylvaleronitrile) was added to a concentration of 0.005 mol / L, and the mixture was polymerized at 45 ° C. for 15 hours under a nitrogen atmosphere. And the polymer was precipitated and recovered. The obtained polymer was redissolved in ethanol, poured into n-hexane, and the precipitated polymer was dried at 75 ° C. for 4 hours to obtain a copolymer of 2-hydroxyethyl methacrylate and N, N-dimethylaminoethyl methacrylate ( Hereinafter, referred to as “HEDM”). HEDM was dissolved in ethanol to a concentration of 1.0 g / L to prepare a HEDM coating solution.

The heat-treated nonwoven fabric is immersed in the HEDM coating solution prepared as described above at 20 ° C. for several tens of seconds to 5 minutes, and then placed in a stainless steel basket and dried at 80 ° C. for 5 minutes to obtain a coated nonwoven fabric. Got. The coated non-woven fabric thus obtained was punched into a square of 7.2 cm × 7.2 cm, and 32 sheets were placed in a square housing (filter container) of 7.2 cm × 7.2 cm × 0.85 cm (thickness). This was inserted to produce a filter unit. The inlet of the filter unit and the blood bag were connected with a 60-cm-long vinyl chloride tube (outer diameter 5 mm, inner diameter 3 mm), and the tube was closed with a clamp. The prepared filter unit was placed in a steam sterilizer (HG-50, manufactured by Hirayama Seisakusho), and steam sterilized at 121 ° C. for 20 minutes. Thus, a leukocyte removal filter provided with a filter material having a coated PET nonwoven fabric was obtained. The filter manufactured in Production Example 1 is referred to as “Filter 1”.

(1-2) Production Example 2
In Production Example 1, a leukocyte removal filter was produced in the same manner as in Production Example 1, except that the heat treatment temperature was changed from 160 ° C to 180 ° C. The filter manufactured in Production Example 2 is referred to as “Filter 2”.

(1-3) Production Example 3
In Production Example 1, a leukocyte removal filter was produced in the same manner as in Production Example 1, except that the heat treatment temperature was changed from 160 ° C to 220 ° C. The filter manufactured in Production Example 3 is referred to as “Filter 3”.

(1-4) Production Example 4
A leukocyte removal filter was produced in the same manner as in Production Example 1, except that the heat treatment temperature was changed from 160 ° C to 140 ° C. The filter manufactured in Production Example 4 is referred to as “Filter 4”.

(1-5) Production Example 5
A leukocyte removal filter was produced in the same manner as in Production Example 1, except that the heat treatment temperature was changed from 160 ° C. to 230 ° C. The filter manufactured in Production Example 5 is referred to as “Filter 5”.

(1-6) Production Example 6
In Production Example 1, a leukocyte removal filter was produced in the same manner as in Production Example 1, except that the heat treatment temperature was changed from 160 ° C. to 250 ° C., and the heat treatment time was changed from 3 minutes to 10 minutes. The filter manufactured in Production Example 6 is referred to as “Filter 6”.

(2) Evaluation method (2-1) Evaluation of filter performance Blood bag containing 400 mL of bovine whole blood and 56 mL of anticoagulant CPD liquid (manufactured by Terumo Corporation, blood bag CPD, composition: sodium citrate hydrate 2.63 w) / V%, citric acid hydrate 0.327 w / v%, glucose 2.32 w / v%, sodium dihydrogen phosphate 0.251 w / v%), and a blood sample was prepared by mixing. . After the blood sample was heated to 4 ° C. using a thermostat, 456 mL of the blood sample in the blood bag was filtered through each filter obtained in the above-mentioned production example by natural fall (fall 60 cm), and the filtered blood was collected in a receiver. . The time from the start of filtration to the emptying of the blood bag was measured and defined as the filtration time.

The white blood cell and red blood cell concentrations of the blood sample before filtration (referred to as “blood before filtration”) and the filtered blood were measured, respectively. Leukocyte concentration was measured by flow cytometry using a flow cytometer LeucoCOUNT kit and FACSCalibur (both manufactured by Becton Dickinson), and red blood cell concentration was measured using a blood cell counter (manufactured by Sysmex, K-4500). It was measured. The leukocyte removal rate (-Log) and the red blood cell recovery rate (%) were calculated by the following equations. In the following formula, a represents the leukocyte concentration of the blood before filtration, b represents the leukocyte concentration of the filtered blood, c represents the erythrocyte concentration of the blood before filtration, and d represents the erythrocyte concentration of the filtered blood. Table 1 shows the evaluation results of each filter.
Leukocyte removal rate = -Log (b / a)
Red blood cell recovery rate (%) = (d / c) × 100

(2-2) DSC Measurement A nonwoven fabric as a filter material was taken out of each filter produced in the above production example. Using a differential scanning calorimeter (EXSTAR6000 DSC6200R, manufactured by Seiko Instruments Inc.), 4.5 to 5.5 mg of the nonwoven fabric taken out was put into an aluminum pan (5 mm in diameter), and the starting temperature was 30 ° C. under a nitrogen atmosphere. The DSC curve was obtained by performing the measurement at the end temperature of 370 ° C. and the heating rate of 10 ° C./min. The DSC curves of the filters obtained in the above production examples are shown in FIGS. 1 to 6, and the temperatures at the maximum values of the first endothermic peak and the second endothermic peak which are the melting points are shown in Table 1. In the DSC curves of FIGS. 1 to 6, the endothermic peak appears as a negative peak, and the minimum value in the DSC curve becomes the maximum value of the endothermic peak.

(2-3) Measurement of elongation A non-woven fabric as a filter material was taken out of each filter produced in the above production example. A test piece having a size of 8 mm in width and 40 mm in length was cut out from the nonwoven fabric taken out. Using a universal testing machine (RTG-1210, manufactured by A & D Corp.), the both ends of the test piece in the TD direction were fixed with chucks, the gap between the chucks was set to 20 mm, the tensile speed was set to 20 mm / min, and the nonwoven fabric was broken. I pulled until I did. The distance between the chucks at the time of breaking was measured, the elongation was obtained from the following equation, and the average value of 10 measurements was calculated. Table 1 shows the measurement results of the elongation of each filter.
Elongation (%) = ((distance between chucks at break of nonwoven fabric−20) / 20) × 100

(3) Results Filters 1 to 3 had the maximum temperature of the second endothermic peak in the range of 155 ° C. or more and 225 ° C. or less, and had high leukocyte removal performance and red blood cell recovery rate. On the other hand, the filter 4 in which the temperature at the maximum value of the second endothermic peak was less than 155 ° C. had lower leukocyte removal performance than the filters 1 to 3. In the case of the filter 5 having a temperature at the local maximum value of the second endothermic peak higher than 225 ° C. and the filter 6 in which the second endothermic peak was not observed, the filter material was broken, and a filter could not be produced.

Claims

A filter material for removing leukocytes,
The filter material has a nonwoven fabric composed of polyester fibers,
In the DSC curve obtained by differential scanning calorimetry (DSC), the nonwoven fabric has a first endothermic peak at a melting point and a second endothermic peak having a maximum value in a temperature region of 155 ° C or more and 225 ° C or less. Characteristic filter material.
The filter material according to claim 1, wherein the nonwoven fabric has an elongation in at least one direction of 15% or more.
The filter material according to claim 2, wherein the elongation is 20% or more.
フィルター The filter material according to any one of claims 1 to 3, wherein the nonwoven fabric comprises 95% by mass or more of the constituent fibers made of polyester fibers.
フィルター The filter material according to any one of claims 1 to 4, wherein the polyester fiber is a polyethylene terephthalate fiber.
(6) The filter material according to any one of (1) to (5), wherein an average fiber diameter of constituent fibers of the nonwoven fabric is 3 μm or less.
フィルター The filter material according to any one of claims 1 to 6, wherein the nonwoven fabric is a meltblown nonwoven fabric.
(8) A leukocyte removal filter, wherein the filter material according to any one of (1) to (7) is disposed in a filter container.
A method for producing a leukocyte removal filter including a filter material having a nonwoven fabric composed of polyester fibers in a filter container,
a) a step of heat-treating the nonwoven fabric composed of polyester fibers in a constrained state at a temperature of 155 ° C. or more and 225 ° C. or less;
b) applying a hydrophilic coating to the non-woven fabric after the heat treatment;
c) arranging a filter material containing the hydrophilic coated nonwoven fabric in a filter container, and sealing the filter container;
d) a step of steam sterilizing the filter material disposed in the filter container at a temperature of 100 ° C. or more and 130 ° C. or less;
A method for producing a leukocyte removal filter, comprising:
10. The method for producing a leukocyte removal filter according to claim 9, wherein the polyester fiber is a polyethylene terephthalate fiber.
11. The method for producing a leukocyte removal filter according to claim 9, wherein an average fiber diameter of constituent fibers of the nonwoven fabric is 3 μm or less.